Does cyproterone acetate (Cyproterone Acetate) in combination with ethinylestradiol (Ethinyl Estradiol) cause depersonalization disorder?

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From the Guidelines

There is no conclusive evidence that cyproterone acetate in combination with ethinylestradiol directly causes depersonalization, though mood changes are known potential side effects of hormonal medications. This combination medication, commonly used for conditions like polycystic ovary syndrome, acne, hirsutism, and as hormone therapy for transgender women, works by altering hormone levels in the body. Cyproterone acetate is an anti-androgen that blocks testosterone effects, while ethinylestradiol is a synthetic estrogen.

Key Points to Consider

  • Mood changes, including depression and anxiety, are known potential side effects of hormonal medications, and these could potentially manifest as feelings of depersonalization in susceptible individuals 1.
  • If someone experiences depersonalization while taking this medication combination, they should not discontinue it abruptly but should consult their healthcare provider promptly.
  • The provider might consider adjusting the dosage, switching to an alternative medication, or referring to mental health support.
  • Individual responses to hormonal medications vary significantly based on factors like genetics, pre-existing mental health conditions, and other medications being taken concurrently.

Relevant Evidence

  • A recent study published in 2024 in Obesity Reviews found that the combination of exenatide, metformin, and a combined oral contraceptive pill (COCP) containing cyproterone acetate and ethinyl estradiol was superior to metformin alone for weight loss and metabolic outcomes in patients with polycystic ovary syndrome 1.
  • However, this study did not report on the incidence of depersonalization as a side effect.
  • Another study published in 2012 in the Journal of Allergy and Clinical Immunology noted that cyproterone acetate has potent antiandrogenic properties and may worsen hereditary angioedema caused by C1 inhibitor deficiency, but did not mention depersonalization as a potential side effect 1.

From the Research

Cyproterone Acetate and Ethinylestradiol Combination

The combination of cyproterone acetate and ethinylestradiol is used to treat various conditions, including hyperandrogenic skin symptoms such as acne and hirsutism.

Efficacy and Safety

  • Studies have shown that this combination is effective in treating severe acne and hirsutism, with a high efficacy rate in sufficiently powered studies 2.
  • The safety and tolerability of this combination have been summarized by the pharmacovigilance risk assessment committee (PRAC) of the European Medicine's Agency's (EMA) 2.
  • Long-term treatment with cyproterone acetate and ethinylestradiol has been shown to be effective and safe in women with hirsutism and/or acne, with a low rate of adverse events 3.

Potential Side Effects

  • There is no direct evidence in the provided studies to suggest that the combination of cyproterone acetate and ethinylestradiol causes depersonalization.
  • However, cyproterone acetate has been shown to have a sedative effect, which may be related to its progestative properties 4.
  • The effects of cyproterone acetate on the hypothalamic pituitary adrenal axis, prolactin, and growth hormone release have been studied, but no conclusive evidence of depersonalization as a side effect has been found 5.

Prescription Appropriateness

  • A population-based study in Italy found that the prescription appropriateness of cyproterone acetate/ethinylestradiol in primary care was generally good, with a low rate of concomitant use with other hormonal contraceptives 6.
  • However, the study did not investigate the potential side effects of depersonalization.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms - a review.

The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, 2017

Research

Experience in the long-term treatment of patients with hirsutism and/or acne with cyproterone acetate-containing preparations: efficacy, metabolic and endocrine effects.

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 1995

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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